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  4. Monte Carlo Track Structure Simulations of Radiation Induced Damage in a Fractal Globule Full Nuclear DNA Model

Monte Carlo Track Structure Simulations of Radiation Induced Damage in a Fractal Globule Full Nuclear DNA Model

A McNamara1*, J Ramos-Mendez2 , J Perl3 , B Faddegon2 , H Paganetti1 , J Schuemann1 , (1) Massachusetts General Hospital & Harvard Med. Sch., Boston, MA, (2) University of California San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, (3) SLAC National Accelerator Laboratory, Menlo Park, CA.

Presentations

(Sunday, 7/29/2018) 4:00 PM - 5:00 PM

Room: Exhibit Hall | Forum 3

Purpose: The cell nucleus, which contains the genome, is the primary radiation target in the cell. Accurate models of the spatial as well as the temporal distribution of energy deposition events induced by radiation, in the form of DNA strand breaks or lesions, on the full DNA structure and its successive evolution, is vital for formulating a comprehensive understanding of the biological effect. Monte Carlo track structure simulations combined with both an accurate model of the nuclear DNA hierarchy as well as repair models have the ability to achieve this goal and predict biological outcomes.

Methods: A full genome model of the cell nucleus, based on a fractal globule was developed for the TOPAS-nBio radiobiology toolkit. TOPAS-nBio is an extension of the Monte Carlo toolkit TOPAS, which wraps and extends Geant4. The genome model incorporates the full hierarchal structure of the DNA; including chromatin territories, chromatin fiber loops, chromatin fibers, nucleosomes and the DNA double helix. A 3D Hilbert space filling curve was used to produce the fractal globule geometry. TOPAS-nBio utilizes the physics and chemistry processes of Geant4-DNA, to model the interaction of particles and their secondary electrons down to low energies (eV), as well as the reaction of reactive oxygen species in the DNA.

Results: DNA damage in the form of single (SSB) and double strand breaks (DSB) were calculated for a range of monoenergetic proton energies. The DSB/SSB yield was found to increase as a function of LET, as expected. Our data was also used in combination with two repair models for comparison.

Conclusion: A nuclear DNA model of a fractal globule was developed in TOPAS-nBio and applied to calculate DSB to SSB yield. Detailed DNA models in combination with track structure simulation and repair models, can further our understanding of the biological effect of DNA.

Keywords

Monte Carlo, Radiobiology, Modeling

Taxonomy

TH- Radiobiology(RBio)/Biology(Bio): RBio- general

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